Up to now no peptide antigens constituting part of pertussis toxin have been identified in the art. Since such antigens have not been provided, it has not been possible to develop diagnostic immunoassay kits comprising such antigens as diagnostic antigens nor to develop vaccines against whooping cough based on such antigens.
Diagnosis of whooping cough with the aid of antigens directed against Bordetella pertussis antibodies or proteins produced by B. pertussis have been published, but as diagnostic antigen there has been used fimbrial hemagglutinin (see e.g. Granstrom, M., Granstroom, G., Lindfors, A., and Askelof, P. 1982. Serologic diagnosis of whooping cough by an enzyme-linked immunosorbent assay using fimbrial hemagglutinin as antigen. J. Infect. Dis. vol 146:741-745), or sonicated B. pertussis bacteria (see e.g. Goodman, Y. E., Wort, A. J. and Jackson, F. L. 1981. Enzyme-linked immunosorbent assay for detection of pertussis immunoglobulin A in nasopharyngeal secretions as an indicator of recent infection. J. Clin. Microbiol. vol. 13:286-292, and Viljanen, M. K., Ruuskanen, O., Granberg, C. and Salmi, T. T. 1982. Serological diagnosis of pertussis: IgM, IgA and IgG antibodies against Bordetella pertussis measured by enzyme-linked immunosorbent assay. Scand. J. Infect. Dis. vol. 14:112-117).
As is well known in the art currently used vaccines against whooping cough are in USA and many other countries based on inactivated Bordetella pertussis bacteria. M. Pittman proposed 1979 that whooping cough was mediated by an exotoxin (pertussis toxin) (see Pittman, M. 1979. Pertussis toxin: The cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis. Rev. Infect. Dis. vol. 1:401-412) and in Japan acellular vaccines comprising inactivated pertussis toxin are currently in use.
Recently the nucleotide sequence of pertussis toxin was published (Locht, C. and Keith, J. M., 1986. Pertussis Toxin Gene: Nucleotide Sequence and Genetic Organization, Science, vol. 232, p. 1258-1264). In this article the authors suggest i.a. that synthetic oligopeptides that include protective epitopes also will be useful in the development of a new generation of vaccines, but there is no teaching or suggestion of such epitopes.
Another recently published article concerning pertussis toxin genes is: Nicosia, A., Perugini, M., Franzini, C., Casagli, M. C., Borri, M. G., Antoni, G., Almoni, M., Neri, P., Ratti, G., and Rappuoli, R., 1986. Cloning and sequencing of the pertussis toxin genes: Operon structure and gene duplication. Proc. Natl. Acad. Sci. USA, vol. 83, 4631-4635. In this publication it is stated i.a. that "Manipulation of the toxin gene by genetic engineering could be a way to produce large amounts of detoxified protein". This is merely a suggestion and no manipulated toxin gene is disclosed.
Yet another publication in this field is: Engstrom, O., Rodmalm, K., Jornvall, H., Lundquist, G., Kalman, M., Simonscits, A., Bartfai, T., Lofdahl, S., and Askelof, P., 1986. Characterization of the N-terminal structure of pertussis toxin subunit S1 and hybridization of oligodeoxyribonucleotide probes with Bordetella pertussis DNA fragment, FEMS Microbiology Letters, vol. 36, 219-223. Also this article makes suggestions, namely, "The gene may also be introduced into other organisms for production of toxin. Sequencing of the gene would allow synthesis of peptides corresponding to the antigenic epitopes of the toxin and hence to the development of a synthetic pertussis vaccine." However, the antigenic epitopes of the pertussis toxin have not been identified, synthesized nor tested.
As regards intradermal skin test compositions, such compositions for testing immunity against pertussis are hitherto not described in the art.